title: Poly (ADP-ribose) polymerase inhibition improves endothelial dysfunction induced by hyperhomocysteinemia in rats.
abstract: BACKGROUND
  We investigated the possible protective effect of poly (ADP-ribose) polymerase (PARP) inhibition in preventing endothelial dysfunction induced by hyperhomocysteinemia (Hhcy).
  
  
  METHODS
  Sprague-Dawley rats were divided into Hhcy group, Hhcy + 3-aminobenzamide(3-AB) group, control group and control + 3-AB group. A high-methionine diet was given to induce hyperhomocysteinemia. In Hhcy + 3-AB and control + 3-AB groups, rats were injected intraperitoneally with 3-AB (inhibitor of PARP). After 45 days, ultrastructural changes of aortas were observed by transmission electron microscope. Vascular reactivity of thoracic aortic rings was measured in organ chambers. PARP activity was detected. The levels of plasma total homocysteine, nitrite/nitrate, endothelin (ET)-1 and malondialdehyde were assayed.
  
  
  RESULTS
  Rats in Hhcy group developed severe hyperhomocysteinemia and significant loss of endothelial function as measured by both vascular rings and levels of nitrite/nitrate and ET-1. Malondialdehyde levels increased significantly in Hhcy rats compared with control rats. 3-AB improved Ach-induced, NO-mediated vascular relaxation and stabilized the level of nitrite/nitrate and ET-1. Obvious improvement of ultrastructure can be observed in Hhcy + 3-AB group.
  
  
  CONCLUSIONS
  These results suggest that pharmacological inhibition of PARP prevents the development of endothelial dysfunction in rats with hyperhomocysteinemia which may represent a novel approach to improve vascular dysfunction associated with hyperhomocysteinemia.
authors.affiliation: Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Yu
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
authors.forename: Jiang-jiao
authors.initials: JJ
authors.lastname: Xie
authors.forename: Meng-yang
authors.initials: MY
authors.lastname: Liao
authors.forename: Rui
authors.initials: R
authors.lastname: Yao
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Ying-jun
authors.initials: YJ
authors.lastname: Ding
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Tang
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Liao
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001549:Benzamides / Q000494:pharmacology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001549:Benzamides; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009569:Nitric Oxide; D008315:Malondialdehyde; C025160:3-aminobenzamide